Linking air pollution exposure to blood-based metabolic features in a community-based aging cohort

Abstract

ABSTRACTLong-term exposure to air pollution has been associated with changes in levels of several metabolites measured in the peripheral blood. However, most work has been conducted in ethnically homogenous populations. We studied the relationship between the plasma metabolome and long-term exposure to three air pollutants: particulate matter (PM) less than 2.5 µm in aero diameter (PM2.5), PM less than 10 µm in aero diameter (PM10) and nitrogen dioxide (NO2) among 107 participants of the Washington Heights and Inwood Community Aging Project (WHICAP) in New York City. Plasma metabolomic profiles were generated using untargeted liquid chromatography coupled with high-resolution mass spectrometry. We estimated the association between each metabolic feature and predicted annual mean exposure to the air pollutants using three approaches: 1. A metabolome wide association study (MWAS) framework; 2. Feature selection using elastic net regression; and 3. A multivariate approach using partial least squares discriminant analysis. Additionally, we identified the pathways enriched by metabolic features associated with exposure through pathway analysis. The samples were collected from 1995 – 2015 and included non-Hispanic white, Caribbean Hispanic, and non-Hispanic Black older adults. Through the MWAS, we found 79 features associated with exposure to PM2.5(false discovery rate at 5%) but none associated with PM10or NO2. Pathway analysis revealed that PM2.5exposure was associated with altered amino acid metabolism, energy production, and oxidative stress response. Six features were found to be associated with PM2.5exposure through all three approaches, annotated as: cysteinylglycine disulfide, a diglyceride, and a dicarboxylic acid. Additionally, we found that the relationship between several features and PM2.5exposure was modified by diet and metabolic diseases. These signals, identified in a neighborhood-representative older population, could help understand the mechanisms through which PM2.5exposure can lead to altered metabolic outcomes in an older population.HIGHLIGHTSLong-term exposure to PM2.5is associated with altered plasma metabolic features in an aging populationThese associations are modified by a dementia diagnosis, history of diabetes, APOE-ε4 allele, and dietPathways related to energy production, amino acid metabolism, and redox homeostasis are associated with exposure to PM2.5GRAPHICAL ABSTRACT